Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNDYSHU)

• DOT Name: Peroxisomal membrane protein 4 (PXMP4)
• Synonyms: 24 kDa peroxisomal intrinsic membrane protein
• Gene Name: PXMP4
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PXMP4_HUMAN
• Pfam ID: PF02466
• Sequence:
  MAAPPQLRALLVVVNALLRKRRYHAALAVLKGFRNGAVYGAKIRAPHALVMTFLFRNGSL
  QEKLWAILQATYIHSWNLARFVFTYKGLRALQSYIQGKTYPAHAFLAAFLGGILVFGENN
  NINSQINMYLLSRVLFALSRLAVEKGYIPEPRWDPFPLLTAVVWGLVLWLFEYHRSTLQP
  SLQSSMTYLYEDSNVWHDISDFLVYNKSRPSN
• Tissue Specificity: Expressed in normal prostate epithelial cells, and androgen-sensitive prostate adenocarcinoma cells. Not expressed in androgen-insensitive prostate adenocarcinoma cells.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway: Class I peroxisomal membrane protein import (R-HSA-9603798)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Posttranslational Modification	[1]
Prostate carcinoma	DISMJPLE	Strong	Posttranslational Modification	[1]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peroxisomal membrane protein 4 (PXMP4).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Peroxisomal membrane protein 4 (PXMP4).	[3]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Peroxisomal membrane protein 4 (PXMP4).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peroxisomal membrane protein 4 (PXMP4).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peroxisomal membrane protein 4 (PXMP4).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peroxisomal membrane protein 4 (PXMP4).	[6]

References

• [1] PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model.Oncogene. 2004 Jan 8;23(1):250-9. doi: 10.1038/sj.onc.1207076.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.